The construction of libraries of fragments of antibody molecules that are expressed on the surface of filamentous bacteriophage and the selection of phage antibodies (Phabs) by binding to antigens have been recognized as powerful means of generating new tools for research and clinical applications. This technology, however, has been mainly used to generate Phabs specific for purified antigens that are available in sufficient quantities of solid-phase dependent selection procedures. The effectiveness of such Phabs in biochemical and functional assays varies; typically, the procedure used to select Phabs determines their utility.
Typically, many antigens of interest are not available in pure form in very large quantities. This clearly limits the utility of Phabs in binding such materials for research and clinical applications. Further, the utility of Phabs in such applications is directly proportional to the purity of the antigens and purification methods to assure the specificity of the isolate Phabs. Human monoclonal antibodies that bind to native cell surface structures are expected to have broad application in therapeutic and diagnostic procedures. An important extension of phage antibody display technology would be a strategy for the direct selection of specific antibodies against antigens expressed on the surface of subpopulations of cells present in a heterogenous mixture. Ideally, such antibodies would be derived from a single highly-diverse library containing virtually every conceivable antibody specificity.